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S47 Enhanced Il-6/ccl3 Signalling In The Plasma Of Patients With Copd
  1. AK Ravi1,
  2. S Khurana1,
  3. A Banyard1,
  4. J Plumb1,
  5. G Booth1,
  6. M Catley2,
  7. L Healy2,
  8. E Smith2,
  9. J Vestbo1,
  10. D Singh1
  1. 1The University of Manchester, Manchester Academic Health Science Centre, University Hospital of South Manchester NHS Foundation Trust, NIHR South Manchester Respiratory and Allergy Clinical Research Facility, Manchester, UK
  2. 2UCB, Slough, UK

Abstract

Rationale IL-6 is a pro-inflammatory cytokine that signals through soluble (sIL-6R/sgp80) and membrane bound (gp80) receptors to promote recruitment of mononuclear cells. IL-6 induces expression of CCL3, a monocytic chemokine. Monocytes are precursors of macrophages and dendritic cells. They can be classified into three subtypes according to surface expression of CD14 (LPS receptor) and CD16 (FcgammaRIII): CD14++CD16-, CD14+CD16+, CD14-CD16++. We measured plasma levels of IL-6, sIL-6R and CCL3 and determined the chemokine receptor expression profile of circulating monocytes in COPD.

Methods 70 COPD patients and 30 healthy controls comprising 15 smokers (S) and 15 healthy non-smokers (HNS) underwent plasma sampling. Levels of IL-6, sIL-6R and CCL3 were determined by multiplex analysis (MSD) of plasma. Multi-colour flow cytometry was performed on whole blood obtained from 32 COPD patients, 8 S and 8 HNS to measure surface expression levels of chemokine receptors CCR1, CCR2, CCR7, CXCR1 and CX3CR1 on CD14++CD16-, CD14+CD16+ and CD14-CD16++ monocytes.

Results COPD patients had the greatest levels of IL-6 and sIL-6R. CCL3 was not detected in any controls, but was present in a subset of COPD patients.% surface expression of the CCL3 receptor CCR1 measured on CD14++CD16- monocytes of COPD patients was greater than those of HNS (p = 0.04). There were no significant differences in expression levels of other chemokine receptors.

Conclusion We report evidence of enhanced IL-6 signalling in the plasma of COPD patients and increased plasma CCL3 in a subset of individuals from this disease group. Furthermore, there was increased CCR1 expression on COPD monocytes. Enhanced IL-6 may co-ordinate the mononuclear component of the inflammatory response in COPD.

Abstract S47 Table 1

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